期刊
JOURNAL OF CELL BIOLOGY
卷 157, 期 1, 页码 137-147出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200108071
关键词
IGF-I; muscular dystrophy; satellite cells; regeneration; protein kinase B
类别
资金
- NIAMS NIH HHS [R01 AR047292, R01AR47292] Funding Source: Medline
Duchenne muscular dystrophy is an X-linked degenerative disorder of muscle caused by the absence of the protein dystrophin. A major consequence of muscular dystrophy is that the normal regenerative capacity of skeletal muscle cannot compensate for increased susceptibility to damage, leading to repetitive cycles of degeneration-regeneration and ultimately resulting in the replacement of muscle fibers with fibrotic tissue. Because insulin-like growth factor 1 (IGF-1) has been shown to enhance muscle regeneration and protein synthetic pathways, we asked whether high levels of muscle-specific expression of IGF-1 in mdx muscle could preserve muscle function in the diseased state. In transgenic mdx mice expressing mlgf-1 (mdx:mlgf(+/+)), we showed that muscle mass increased by at least 40% leading to similar increases in force generation in extensor digitorum longus muscles compared with those from mdx mice. Diaphragms of transgenic mdx:mlgf(+/+) exhibited significant hypertrophy and hyperplasia at all ages observed. Furthermore, the IGF-1 expression significantly reduced the amount of fibrosis normally observed in diaphragms from aged mdx mice. Decreased myonecrosis was also observed in diaphragms and quadriceps from mdx:mlgf(+/+) mice when compared with age-matched mdx animals. Finally, signaling pathways associated with muscle regeneration and protection against apoptosis were significantly elevated. These results suggest that a combination of promoting muscle regenerative capacity and preventing muscle necrosis could be an effective treatment for the secondary symptoms caused by the primary loss of dystrophin.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据